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B cell depletion in murine lupus using cytotoxic T lymphocytes in vivo: Feasibility and benefit

2020; Elsevier BV; Volume: 353; Linguagem: Inglês

10.1016/j.cellimm.2020.104117

1090-2163

Kateryna Soloviova, Irina Puliaeva, Maksym Puliaiev, Roman Puliaev, Charles S. Via,

Systemic Lupus Erythematosus Research

Given the promising results in human lupus with B cell depletion, we tested whether in vivo cytotoxic T lymphocyte (CTL) could eliminate autoreactive B cells in the setting of murine lupus. Using the parent-into-F1 (P → F1) model to generate CTL that eliminate B cells, we found that transfer of NZB parental splenocytes into lupus-prone female NZB/W F1 mice resulted in profound B cell reduction whereas NZW → F1 mice exhibited defective B cell elimination. Using pre-disease or early disease B/W mice as hosts, NZB → F1 mice exhibited B cell depletion and improved proteinuria but no improvement in survival whereas NZW → F1 mice had significantly reduced proteinuria and prolonged survival. Thus, despite the defective IL-2 environment in B/W F1 mice, generation of CTL and B cell depletion is feasible in NZB → F1 mice. The surprising increase in survival for NZW → F1 mice despite defective B cell elimination suggests that NZW splenocytes may contain a beneficial down regulatory cell.